Water → 4-benzyl-6-[2-cyclopropyl-5-((2S,3S,4R,5R,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yl)-benzyl]-3,4-dihydro-2H-benzo[1,4]oxazine

HRID 72617

反応式

HRID 72617 の反応式
[CH2:1]([N:8]1[C:13]2[CH:14]=[C:15]([CH2:18][C:19]3[CH:24]=[C:23]([C@H:25]4[C@H:30]([O:31][CH2:32][C:33]5[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=5)[C@@H:29]([O:39][CH2:40][C:41]5[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=5)[C@H:28]([O:47][CH2:48][C:49]5[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=5)[C@@H:27]([CH2:55][O:56][CH2:57][C:58]5[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=5)[O:26]4)[CH:22]=[CH:21][C:20]=3Br)[CH:16]=[CH:17][C:12]=2[O:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:65]1(B(O)O)[CH2:67][CH2:66]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([N:8]1[C:13]2[CH:14]=[C:15]([CH2:18][C:19]3[CH:24]=[C:23]([C@H:25]4[C@H:30]([O:31][CH2:32][C:33]5[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=5)[C@@H:29]([O:39][CH2:40][C:41]5[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=5)[C@H:28]([O:47][CH2:48][C:49]5[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=5)[C@@H:27]([CH2:55][O:56][CH2:57][C:58]5[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=5)[O:26]4)[CH:22]=[CH:21][C:20]=3[CH:65]3[CH2:67][CH2:66]3)[CH:16]=[CH:17][C:12]=2[O:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

7

反応物 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 529135254-benzyl-6-[2-bromo-5-((2S,3S,4R,5R,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yl)-benzyl]-3,4-dihydro-2H-benzo[1,4]oxazine

生成物 1

HCID 529135264-benzyl-6-[2-cyclopropyl-5-((2S,3S,4R,5R,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yl)-benzyl]-3,4-dihydro-2H-benzo[1,4]oxazine収率 95%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 22272177Toluene water溶媒

反応条件

温度
100 °C

実験手順

To a stirred solution of 4-benzyl-6-[2-bromo-5-((2S,3S,4R,5R,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yl)-benzyl]-3,4-dihydro-2H-benzo[1,4]oxazine (0.35 g, 0.38 mmol) in toluene:water (10:1 mixture, 10 mL) was added cyclopropylboronic acid (49.2 mg, 0.5731 mmol) tricyclohexylphosphine (26.7 mg, 0.0955 mmol), and potassium phosphate (0.28 g, 1.34 mmol). The reaction mixture was degassed for 45 min then palladium (II) acetate (8.5 mg, 0.03821 mmol) was added. After heating overnight at 100° C., the reaction mixture was cooled to room temperature and water (20 mL) was added. The resulting mixture was extracted with ethyl acetate (2×25 mL), washed with water and brine, then dried over sodium sulfate, concentrated and purified by column chromatography to furnish 4-benzyl-6-[2-cyclopropyl-5-((2S,3S,4R,5R,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yl)-benzyl]-3,4-dihydro-2H-benzo[1,4]oxazine (317 mg). The product was taken up for the next step without characterization.

後処理

  1. customThe reaction mixture was degassed for 45 min
  2. temperaturethe reaction mixture was cooled to room temperature
  3. extractionThe resulting mixture was extracted with ethyl acetate (2×25 mL)
  4. washwashed with water and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. custompurified by column chromatography

出典と根拠

ORDレコード
ord-6678cb7f5c784103b1b4fdd366803d9e
出典データセット
uspto-grants-2014_09
特許番号
US08828951B2

関連ノート

読み込み中…